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Antizyme suppression leads to an increment of the cellular redox potential and an induction of HIF‐1α: Its involvement in resistance to γ‐radiation
Author(s) -
Kim Jin Sik,
Kim Tae Lim,
Cho Eun Wie,
Paik Sang Gi,
Chung Hai Won,
Kim In Gyu
Publication year - 2008
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.49
Subject(s) - glutathione , nicotinamide adenine dinucleotide phosphate , isocitrate dehydrogenase , ornithine decarboxylase , reactive oxygen species , nicotinamide adenine dinucleotide , ornithine decarboxylase antizyme , glutathione disulfide , intracellular , polyamine , biochemistry , programmed cell death , chemistry , cell growth , microbiology and biotechnology , nad+ kinase , biology , enzyme , apoptosis , oxidase test
The mammalian antizyme (AZ) promotes ubiqutin‐independent degradation of ornithine decarboxylase, a key enzyme in polyamine biosynthesis. This study shows that AZ suppression in human lung carcinoma A549 cells caused growth defects and death, but made the cells resistant to DNA damaging agents such as γ‐radiation and cisplatin. In these cells, the cellular redox potential (glutathione/glutathione disulfide [GSH/GSSG] ratio) was increased and thus intracellular reactive oxygen species were severely diminished, which might cause growth defects and cell death. The increase of cellular redox potential was mainly caused by dramatic increase of the cytoplasmic nicotinamide adenine dinucleotide phosphate (NADP) + ‐dependent isocitrate dehydrogenase, which generates the reducing equivalents NADPH. In the AZ‐suppressed cells, the hypoxia inducible factor 1α (HIF‐1α) was also increased. As in other cases which showed an increment of HIF‐1α and the cellular redox potential, the AZ‐suppressed cells showed resistance to γ‐radiation and anticancer drugs. Therefore, these facts might be considered as important for the use of radio‐ and chemotherapy on tumor cells which show an unbalance in their polyamine levels. © 2008 IUBMB IUBMB Life, 60(6): 402–409, 2008